Review Hijacking the Chromatin Remodeling Machinery: Impact of SWI/SNF Perturbations in Cancer Bernard Weissman 1 and Karen E. Knudsen 2 1 Department of Pathology and Laboratory and Lineberger Cancer Center, University of North Carolina, Chapel Hill, North Carolina and 2 Department of Cancer Biology, Department of Urology, and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania Abstract There is increasing evidence that alterations in chromatin re-modeling play a significant role in human disease. The SWI/ SNF chromatin remodeling complex family mobilizes nucleo-somes and functions as a master regulator of gene expression and chromatin dynamics whose functional specificity is driv-en by combinatorial assembly of a central ATPase and associ-ation with 10 to 12 unique subunits. Although the biochemical consequence of SWI/SNF in model systems has been extensive-ly reviewed, the present article focuses on the evidence linking SWI/SNF perturbations to cancer initiation and tumor pro-gression in human disease. [Cancer Res 2009;69(21):8223 – 30] Introduction The SWI/SNF family of chromatin remodeling complexes are master regulators of transcription factor action and resultant gene expression programs. SWI/SNF complexes are large, ∼ 2-MDa mul-ti-subunit conglomerates that serve to either enhance or suppress gene transcription through mobilization of nucleosomes (1, 2). In-triguingly, mounting evidence supports the paradigm that specific-ity of SWI/SNF action evolves through combinatorial assembly of 10 to 12 subunits, and that “ imbalances ” in subunit composition are frequently observed in human cancers. Although the functions of SWI/SNF in transcriptional control and development have been extensively reviewed (1 – 6), the present study will focus exclusively

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